The recent NAS PM Research Priorities report highlighted the need to "investigate through toxicological and epidemiological studies the interactions between particulate matter and gaseous co-pollutants introducing harmful short-term and long-term exposures and resolving adverse health effects." Two prospective cohort studies (Harvard 6-cities and American Cancer Society) showed significant excess annual total, cardiopulmonary, and lung cancer mortality in proportion to annual average fine particle mass concentration (PM2.5) and/or sulfate aerosol concentration. The specific aims of this research are to test the hypotheses that: 1) gaseous pollutants play a role in the excess annual cardiopulmonary mortality that has been associated with PM2.5 and sulfate; 2) lung cancer mortality rates are enhanced by particulate air pollution; and 3) the mortality that has been associated with PM results in substantial life shortening. The overall objective of this research is to answer these questions by a major expansion of the previously published ACS cohort mortality-air pollution investigation including a two-fold increase in the number of death records that will be used in the analyses. The technical approaches to be applied for this research are extensions of those used in the previously published ACS study. The multiple pollutant regression analyses will be based on the Cox proportional hazards model. For ambient pollutant concentration data sets, we will use the EPA's AIRS database, the fine particle database from EPA's Inhalable Particulate (IP) network, nationwide historical weather and visibility records, and in-house data for artifact-free PM2.5 sulfate in 66 U.S. communities in 1990. The results expected are more comprehensive and detailed analyses of the mortality experience of the ACS prospective cohort population in relation to ambient concentrations of air pollutants in the communities in which they reside. In addition to the PM2.5 analyses in relation to annual mortality rates, we will produce proportional hazards analyses using PM2.5, sulfate, 03, CO, SO2, and NO2 in order to determine the independent and/or combined effects of the major components of the ambient pollution mixture. By expanding the scope of pollutants and the consideration of other modeling approaches to better account for the influences of personal risk factors, we expect to clarify the roles of specific pollutant factors and to more precisely determine rates for specific annual mortality causes, the influence of individual risk factors among the population segments, and the extent of life-span reduction attributable to exposure to air pollutants.